Insulin binding to circulating monocytes has been evaluated in different conditions of insulin resistance (acromegaly, ataxia telangiectasia, hypercortisolism, lipoatrophic diabetes) as well as in patients with insulinoma and even in normal subjects. The insulin receptor has been characterized also in circulating erythrocytes from normals and from patients with anorexia nervosa, ataxia telangiectasia, hypercorticolism, and lipoatrophic diabetes. Insulin receptor concentration is inversely correlated with the concentration of plasma insulin. The affinity of receptor can be reduced by the presence of antireceptor antibodies, or can be increased in acromegaly or changed by ingestion of glucose in normal subjects. The binding defect observed in patients with anti-receptor antibodies can be reversed both in vivo and in vitro by removing the antibodies.